Skip to main content
Log in

Synthesis and in vitro antimicrobial activity of some newer quinazolinone–sulfonamide linked hybrid heterocyclic entities derived from glycine

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

A novel series of 4-(amino or acetamido)-N-{[3-(substituted aryl)-4-oxo-3,4-dihydroquinazolin-2-yl]-methyl}benzenesulfonamide derivatives (119) were designed to assimilate 4-quinazolone and sulfonamide moieties in a single molecular framework. To derive entitled hybrid entities with structural diversity, an efficient multi-step synthetic approach initiated from glycine was developed, which involves milder conditions for emphasizing steps viz., reaction in aqueous-media, phosphazo-method of condensation, base mediated selective ester-cleavage, along with key-step, rapid and improved Grimmel’s hetero-cyclization method. The structure of the synthesized compounds was confirmed by physico-chemical characteristics and spectroscopic investigations. All these compounds were screened for their in vitro antimicrobial activity. The minimum inhibitory concentrations of the synthesized compounds against various bacteria (S. aureus, B. cereus, E. coli, K. pneumonia, P. aeruginosa) and fungus (A. niger, C. albicans) was measured by broth microdilution assay. Further, results on the preliminary biological activity indicated that most of the screened compounds have displayed varied degree of inhibitory actions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Scheme 2

Similar content being viewed by others

References

  • Anand N, (1996) Therapeutic agents: sulfonamides and sulfones. In: Wolff ME (ed) Burger’s Medicinal Chemistry and Drug Discovery, vol 2. Wiley, Hoboken, pp 527–544

  • Anderson MO, Moser J, Sherrill J, Guy KR (2004) A convenient procedure for parallel ester hydrolysis. Synlett 13:2391–2393

    Google Scholar 

  • Calaza MI, Cativiela C (2010) Heterocycles from amino acids. In: Hughes AB (ed) Amino acids, peptides and proteins in organic chemistry—building blocks, catalysis and coupling chemistry, vol 3. Wiley-VCH Verlag GmbH & Co, Weinheim, pp 83–114

    Google Scholar 

  • Chohan ZH, Youssoufi MH, Jarrahpour A, Ben Hadda T (2010) Identification of antibacterial and antifungal pharmacophore sites for potent bacteria and fungi inhibition: indolenyl sulfonamide derivatives. Eur J Med Chem 45:1189–1199

    Article  CAS  PubMed  Google Scholar 

  • Cohen ML (1992) Epidemiology of drug resistance: implications for a post-antimicrobial era. Science 257:1050–1055

    Article  CAS  PubMed  Google Scholar 

  • Connolly DJ, Cusack D, O’Sullivan TP, Guiry PJ (2005) Synthesis of quinazolinones and quinazolines. Tetrahedron 61:10153–10202

    Article  CAS  Google Scholar 

  • Dixit RB, Vanparia SF, Patel TS, Jagani CL, Doshi HV, Dixit BC (2010) Synthesis and antimicrobial activities of sulfonohydrazide-substituted 8-hydroxyquinoline derivative and its oxinates. Appl Organomet Chem 24:408–413

    CAS  Google Scholar 

  • Domínguez J, Leónb C (2006) Amino acids in the synthesis of triazinoquinazolinones. IUPAC web resource. http://www.oldiupacorg/publications/cd/medicinal_chemistry/Practica-V-7pdf. Accessed 2 Feb 2013

  • El-Sharief AMSh, Ammar YA, Zahran MA, Ali AH, El-Gaby MSA (2001) Aminoacids in the synthesis of heterocyclic systems: the synthesis of triazinoquinazolinones, triazepinoquinazolinones and triazolinoquinazolinones of potential biological interest. Molecules 6:267–278

    Article  CAS  Google Scholar 

  • Giri RS, Thaker HM, Giordano T, Williams J, Rogers D, Sudersanam V, Vasu KK (2009) Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-κB and AP-1 mediated transcription activation and as potential anti-inflammatory agents. Eur J Med Chem 44:2184–2189

    Article  CAS  PubMed  Google Scholar 

  • Grimmel HW, Guenther A, Morgan JF (1946a) Phosphazo compounds and their use in preparing amides. J Am Chem Soc 68:539–542

    Article  CAS  Google Scholar 

  • Grimmel HW, Guenther A, Morgan JF (1946b) A new synthesis of 4-quinazolones. J Am Chem Soc 68:542–543

    Article  CAS  PubMed  Google Scholar 

  • Grover G, Kini SG (2006) Synthesis and evaluation of new quinazolone derivatives of nalidixic acid as potential antibacterial and antifungal agents. Eur J Med Chem 41:256–262

    Article  CAS  PubMed  Google Scholar 

  • Hirota S, Sakai T, Kitamura N, Kubokawa K, Kutsumura N, Otani T, Saito T (2010) Synthesis of nitrogen heterocycle-fused 1,2,4-benzothiadiazine-1,1-dioxide, quinazolinone, and pyrrolidinone derivatives with a guanidine joint via sequential aza-Wittig reaction/intramolecular NH-addition cyclization/nucleophilic substitution ring closure methodology, using functionalized carbodiimides as key intermediates. Tetrahedron 66:653–662

    Article  CAS  Google Scholar 

  • Horton DA, Bourne GT, Smythe ML (2003) The combinatorial synthesis of bicyclic privileged structures or privileged substructures. Chem Rev 103:893–930

    Article  CAS  PubMed  Google Scholar 

  • Itoh F, Yoshioka Y, Yukishige K, Yoshida S, Wajima M, Ootsu K, Akimoto H (1998) Non-glutamate type pyrrolo[2,3-d]pyrimidine antifolates II. Synthesis and antitumor activity of N5-substituted glutamine analogs. Chem Pharm Bull 44(8):1498–1509

    Article  Google Scholar 

  • Jagani CL, Sojitra NA, Vanparia SF, Patel TS, Dixit RB, Dixit BC (2011) A convergent microwave assisted synthesis of 4-amino-N-(4-oxo-2-substituted-4H-quinazolin-3-yl)-benzenesulfonamide derivatives. Arkivoc IX:221–237

    Google Scholar 

  • Jagani CL, Sojitra NA, Vanparia SF, Patel TS, Dixit RB, Dixit BC (2012a) Microwave promoted synthesis and antimicrobial activity of 3-thiazole substituted 2-styryl-4(3H)-quinazolinone derivatives. J Saudi Chem Soc 16(4):363–369

    Google Scholar 

  • Jagani CL, Vanparia SF, Patel TS, Dixit RB, Dixit BC (2012b) A comparative study of solution phase as well as solvent free microwave assisted syntheses of 3-benzothiazole/isoxazole substituted 2-styryl-4(3H)-quinazolinones. Arkivoc VI:281–294

    Google Scholar 

  • Kalusa A, Chessum N, Jones K (2008) An efficient synthesis of 2,3-diaryl (3H)-quinazolin-4-ones via imidoyl chlorides. Tetrahedron Lett 49:5840–5842

    Article  CAS  Google Scholar 

  • Kashaw SK, Kashaw V, Mishra P, Jain NK, Stables JP (2009) Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea. Eur J Med Chem 44:4335–4343

    Article  CAS  PubMed  Google Scholar 

  • Larksarp C, Alper H (2000) Palladium-catalyzed cyclocarbonylation of o-iodoanilines with heterocumulenes: regioselective preparation of 4(3H)-quinazolinone derivatives. J Org Chem 65:2773–2777

    Article  CAS  PubMed  Google Scholar 

  • Liu J-F (2007) Rapid syntheses of biologically active quinazolinone natural products using microwave technology. Curr Org Synth 4:223–237 (and references cited therein)

    Google Scholar 

  • Liu J-F, Lee J, Dalton AM, Bi G, Yu L, Baldino CM, McElory E, Brown M (2005) Microwave-assisted one-pot synthesis of 2,3-disubstituted 3H-quinazolin-4-ones. Tetrahedron Lett 46:1241–1244

    Article  CAS  Google Scholar 

  • Madkour HMF (2004) Reactivity of 4H-3,1-benzoxazin-4-ones towards nitrogen and carbon nucleophilic reagents: applications to the synthesis of new heterocycles. Arkivoc I:36–54

    Google Scholar 

  • Meyyanathan SN, Ramu M, Suresh B (2010) Synthesis, antimalarial and antibacterial activities of 3-amino acid- and aryl amine-substituted 2-methyl-3H-quinalzolin-4-ones. Med Chem Res 19:993–999

    Article  CAS  Google Scholar 

  • Mhaske SB, Argade NP (2006) The chemistry of recently isolated naturally occurring quinazolinone alkaloids. Tetrahedron 62:9787–9826

    Article  CAS  Google Scholar 

  • Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH (1995) Antimicrobial agents and susceptibility testing. In: Woods GL, Washington JA (eds) Manual of clinical microbiology. The American Society for Microbiology, Washington, DC

    Google Scholar 

  • Pandey SK, Singh A, Singh A, Nizamuddin A (2009) Antimicrobial studies of some novel quinazolinones fused with [1,2,4]-triazole, [1,2,4]-triazine and [1,2,4,5]-tetrazine rings. Eur J Med Chem 44:1188–1197

    Article  CAS  PubMed  Google Scholar 

  • Panneerselvam P, Rather BA, Reddy DRS, Kumar NR (2009) Synthesis and anti-microbial screening of some Schiff bases of 3-amino-6,8-dibromo-2-phenylquinazolin-4(3H)-ones. Eur J Med Chem 44:2328–2333

    Article  CAS  PubMed  Google Scholar 

  • Patil DA, Patil PO, Patil GB, Surana SJ (2011) Synthesis of 2,3-disubstituted-quinazolin-4-(3H)-ones. Mini Rev Med Chem 11(8):633–641

    Article  CAS  PubMed  Google Scholar 

  • Rabilloud G, Sillion B (1980) Synthesis of 4H-3,1-benzoxazin-4-ones and 4-(3H)quinazolinones from anthranilic acids and their derivatives by the use of triphenyl phosphite and pyridine. J Heterocycl Chem 17:1065–1068

    Article  CAS  Google Scholar 

  • Rao DA, Shankar RC, Reddy BP, Reddy MV (1985) Synthesis and biological activities of certain derivatives of 3-aryl-4(3H)-quinazolinones. Part II. J Indian Chem Soc 62:234–237

    CAS  Google Scholar 

  • Reddy PS, Reddy PP, Vasantha T (2003) A review on 2-heteryl- and heteroalkyl-4(3H)-quinazolinones. Heterocycles 60(1):183–186

    Article  CAS  Google Scholar 

  • Reynolds EJEF (ed) (1996) Martindale: the extra pharmacopoeia, 31st edn. The Royal Pharmaceutical Society, London

    Google Scholar 

  • Salehi P, Dabiri M, Zolfigol MA, Baghbanzadeh M (2005) A new approach to the facile synthesis of mono- and disubstituted quinazolin-4(3H)-ones under solvent-free conditions. Tetrahedron Lett 46:7051–7053

    Article  CAS  Google Scholar 

  • Saravanan G, Alagarsamy V, Prakash CR (2012) Synthesis, analgesic, anti-inflammatory, and in vitro antimicrobial activities of some novel quinazolin-4(3H)-one derivatives. Med Chem Res. doi:10.1007/s00044-012-0037-7

  • Sardina FJ, Rapoport H (1996) Enantiospecific synthesis of heterocycles from α-amino acids. Chem Rev 96:1825–1872

    Article  CAS  PubMed  Google Scholar 

  • Schröder J, Henke A, Wenzel H, Brandstetter H, Stammler HG, Stammler A, Pfeiffer WD, Tschesche H (2001) Structure-based design and synthesis of potent matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. J Med Chem 44:3231–3243

    Article  PubMed  Google Scholar 

  • Silverman RB (1992) The organic chemistry of drug design and drug action. Academic Press, London

    Google Scholar 

  • Smith DA, Jones RM (2008) The sulfonamide group as a structural alert: a distorted story? Curr Opin Drug Discov Dev 11:72–79

    CAS  Google Scholar 

  • Storelli S, Verdijk P, Verzijl D, Timmerman H, van de Stolpe AC, Tensen CP, Smit MJ, De Esch IJP, Leurs R (2005) Synthesis and structure-activity relationship of 3-phenyl-3H-quinazolin-4-one derivatives as CXCR3 chemokine receptor antagonists. Bioorg Med Chem Lett 15:2910–2913

    Article  CAS  PubMed  Google Scholar 

  • Thierry B, Elizabeth C (2007) Microwave-assisted synthesis of bioactive quinazolines and quinazolinones. Comb Chem High Throughput Screen 10:903–917

    Article  Google Scholar 

  • Tiwari VK, Kale RR, Mishra BB, Singh A (2008) A facile one-pot MW approach for N3-(heteroaryl-2′-yl)- 2-thioxo-2,3-dihydro-1H-quinazolin-4-one. Arkivoc (xiv):27–36

  • Vanparia SF, Patel TS, Sojitra NA, Jagani CL, Dixit BC, Patel PS, Dixit RB (2010) Synthesis, characterization and antimicrobial study of novel 4-{[(8-hydroxyquinolin-5-yl)methyl]amino}benzenesulfonamide and its oxinates. Acta Chim Slov 57:660–667

    CAS  PubMed  Google Scholar 

  • Wasfy AAF (2002) Studies on quinazolines. Part I. Annelation to the quinazoline ring utilizing amino acid esters. Phosphorus Sulfur Silicon Relat Elem 177:1349–1358

    Article  CAS  Google Scholar 

  • Wilden JD (2010) The sulfonamide motif as a synthetic tool. J Chem Res 34:541–548

    Article  CAS  Google Scholar 

  • Witt A, Bergman J (2003) Recent developments in the field of quinazoline chemistry. Curr Org Chem 7:659–677

    Article  CAS  Google Scholar 

  • Xie J, Seto CT (2007) A two stage click-based library of protein tyrosine phosphatase inhibitors. Bioorg Med Chem 15:458–473

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xu W, Fu H (2011) Amino acids as the nitrogen-containing motifs in copper-catalyzed domino synthesis of N-heterocycles. J Org Chem 76:3846–3852

    Article  CAS  PubMed  Google Scholar 

  • Xue S, McKenna J, Shieh WC, Repič O (2004) A facile synthesis of C2, N3-disubstituted-4-quinazolone. J Org Chem 69:6474–6477

    Article  CAS  PubMed  Google Scholar 

  • Zhichkin P, Kesicki E, Treiberg J, Bourdon L, Ronsheim M, Ooi HC, White S, Judkins A, Fairfax D (2007) A novel highly stereoselective synthesis of 2,3-disubstituted 3H-quinazoline-4-one derivatives. Org Lett 9:1415–1418

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the financial support received from the University Grants Commission (New Delhi, India) for this work under the scheme of Major Research Project [UGC File No. 34301/2008 (SR)]. We are grateful to the principal of V. P. & R. P. T. P. Science College (VV Nagar) for providing necessary research facilities to carry out entitled work. We are also thankful to the Director(s) of various organizations (SICART, Oxygen HealthCare Pvt. Ltd.) for the analytical services at discounted rate, and their analysts for co-operation. We express our sincere thanks to Prof. P.H. Parsaniya, Head, Chemistry Department, Saurashtra University (Rajkot) for permitting SFV (Project Fellow) to access SciFinder database.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bharat C. Dixit.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 284 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vanparia, S.F., Patel, T.S., Dixit, R.B. et al. Synthesis and in vitro antimicrobial activity of some newer quinazolinone–sulfonamide linked hybrid heterocyclic entities derived from glycine. Med Chem Res 22, 5184–5196 (2013). https://doi.org/10.1007/s00044-012-0320-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-012-0320-7

Keywords

Navigation